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Tide Fluor™ 2 (TF2) family has the spectral properties similar to those of fluoresceins and Alexa Fluor® 488 (Alexa Fluor® is the trademark of Invitrogen). TF2 phosphoramidite enables the oligo labeling with the similar spectral properties and photostability of Alexa Fluor® 488 using the well established phosphoramidite chemistry. Compared to fluoresceins TF2 family has much stronger fluorescence and higher photostability. Additionally their fluorescence is pH-independent from pH 3 to 11. These characteristics make this new dye family a superior alternative to fluoresceins. TF2-labeled peptides and nucleotides exhibit much stronger fluorescence and higher photostability than the ones labeled with FITC or FAM. In addition, TF2 is an excellent replacement to the expensive Alexa Fluor® 488 due to their similar spectral properties, pH dependence and photostability. In pairing with our Tide Quencher™ 2 (TQ2), a variety of FRET peptides and nucleotides can be developed for detecting proteases and molecular beacons with enhanced sensitivity and stability.